Abstract

BACKGROUND. The idea that increasing salt intake increases drinking and urine volume is widely accepted. We tested the hypothesis that an increase in salt intake of 6 g/d would change fluid balance in men living under ultra-long-term controlled conditions.

METHODS. Over the course of 2 separate space flight simulation studies of 105 and 205 days’ duration, we exposed 10 healthy men to 3 salt intake levels (12, 9, or 6 g/d). All other nutrients were maintained constant. We studied the effect of salt-driven changes in mineralocorticoid and glucocorticoid urinary excretion on day-to-day osmolyte and water balance.

RESULTS. A 6-g/d increase in salt intake increased urine osmolyte excretion, but reduced free-water clearance, indicating endogenous free water accrual by urine concentration. The resulting endogenous water surplus reduced fluid intake at the 12-g/d salt intake level. Across all 3 levels of salt intake, half-weekly and weekly rhythmical mineralocorticoid release promoted free water reabsorption via the renal concentration mechanism. Mineralocorticoid-coupled increases in free water reabsorption were counterbalanced by rhythmical glucocorticoid release, with excretion of endogenous osmolyte and water surplus by relative urine dilution. A 6-g/d increase in salt intake decreased the level of rhythmical mineralocorticoid release and elevated rhythmical glucocorticoid release. The projected effect of salt-driven hormone rhythm modulation corresponded well with the measured decrease in water intake and an increase in urine volume with surplus osmolyte excretion.

(A) Time series of 24-hour sodium excretion (UNaV), urine volume, and water intake in the representative subject 54 during the 205-day experiment. (B) Average fluid intake per salt intake phase in all 10 subjects (n = 1,646). (C) Quantification of the changes in fluid intake per salt intake phase or per 24-hour UNaV tertile. (D) Average urine volume per salt intake phase in the same subjects (n = 1,644). (E) Quantification of the changes in urine volume per salt intake phase or per UNaV tertile. (F) Average 24-hour UNaV per salt intake phase in the same subjects (n = 1,646). (G) Quantification of the changes in UNaV per salt intake phase or per UNaV tertile. Data are expressed as the average ± SD (B, D, and F) or as the Δ change ± SEM (C, E, and G). Data were statistically analyzed by mixed linear model. Details on statistical analysis for Figure 1 are provided in the Supplemental Materials (page 28).